Identification and dietary relevance of antioxidants from raspberry

In this paper we review the current literature on antioxidants from fruit of red raspberry (Rubus idaeus) and place these in context concerning what is known from other food species. The review concentrates on the methods of antioxidant testing, the diversity of antioxidants in raspberry, effects of ripeness, cultivar, storage and processing techniques, and the bioavailability of raspberry antioxidants in humans after eating the fruit. It is clear that raspberry, like several other fruits and vegetables such as tomato, strawberry, kiwi and broccoli, represents a valuable contrasting source of potentially healthy compounds and can represent an important component of a balanced diet.     

Physiological and metabolic effects of dietary fiber

William Beaumont noted the gastric effects of vegetable fiber and suggested that dietary fiber may provide health benefits. In the last decade investigators documented the physiological effects of fiber on gastric emptying, intestinal nutrient absorption rates, and colon function. Further clinical investigation and much more of the type of repetitive observations pioneered by Beaumont are required to definitively establish the physiological effects of fiber on gastrointestinal physiology. High-fiber intake provides well-established benefits for persons with diabetes: it lowers insulin requirements, provides better control of blood glucose, and reduces serum lipids. Foods rich in soluble fiber, such as oat or bean products, lower cholesterol significantly for persons with hypercholesterolemia and for healthy young subjects. High-fiber foods also lower serum triglycerides and blood pressure. Several studies indicate that high intake of fiber protects against coronary heart disease.     

Physiological relevance of sphingolipid activator proteins in cultured human fibroblasts

The physiological degradation of several membrane-bound glycosphingolipids (GSLs) by water-soluble lysosomal exohydrolases requires the assistance of sphingolipid activator proteins (SAPs). Four of these SAPs are synthesized from a single precursor protein (prosaposin). Inherited deficiency of this precursor results in a rare disease in humans with an accumulation of ceramide (Cer) and glycolipids such as glucosylceramide and lactosylceramide (LacCer). In a previous study, we have shown that human SAP-D stimulates the lysosomal degradation of Cer in precursor deficient cells. In order to study the role of SAPs (or saposins) A-D in cellular GSL catabolism, we recently investigated the catabolism of exogenously added [(3)H]labeled ganglioside GM1, Forssman lipid, and endogenously [(14)C]labeled GSLs in SAP-precursor deficient human fibroblasts after the addition of recombinant SAP-A, -B, -C and -D. We found that activator protein deficient cells are still able to slowly degrade gangliosides GM1 and GM3, Forssman lipid and globotriaosylceramide to a significant extent, while LacCer catabolism critically depends on the presence of SAPs. The addition of either of the SAPs, SAP-A, SAP-B or SAP-C, resulted in an efficient hydrolysis of LacCer.     

Physiological and pathological relevance of cell competition in fly to mammals

In multicellular organisms, incidentally emerging suboptimal cells are removed to maintain homeostasis of tissues. The unfavorable cells are excluded by a process termed cell competition whereby the resident normal cells actively eliminate the unfit cells of the identical lineage. Although the phenomenon of cell competition was originally discovered in Drosophila, a number of recent studies have provided implications of cell competition in tissue regeneration, development and oncogenesis in mammals. Here the roles of cell competition in fly to mammals are discussed.     

Physiological relevance of telomeric G-quadruplex formation: a potential drug target

The concept of a G-quartet, a unique structural arrangement intrinsic to guanine-rich DNA, was first introduced by Gellert and colleagues over 40 years ago. For decades, it has been uncertain whether the G-quartet and the structure that it gives rise to, the G-quadruplex, are purely in vitro phenomena. Nevertheless, the presence of signature G-rich motifs in the eukaryotic genome, and the plethora of proteins that bind to, modify or resolve this nucleic acid structure in vitro have provided circumstantial evidence for its physiological relevance. More recently, direct visualisation of G-quadruplex DNA at native telomeres was achieved, bolstering the evidence for its existence in the cell. Furthermore, G-quadruplex folded telomeric DNA has been found to perturb telomere function and to impede the action of telomerase, an enzyme overexpressed in >85% of human cancers, hence opening up a novel avenue for cancer therapy in the form of G-quadruplex stabilising agents.     

Physiological and pathological relevance of extracellular NM23/NDP kinases

The nm23 gene is overexpressed in many hematological malignancies and other neoplasms. Some tumor cell lines that overexpress NM23 secrete this protein into extracellular environment. In this study, we found that the serum concentration of NM23-H1 protein was significantly higher in patients with various hematological malignancies. The serum level of NM23-H1 protein was clinically useful as a prognostic factor in malignant lymphoma and acute myelogeneous leukemia (AML). The level of NM23-H1 protein in all of the normal serum samples examined was lower than 10 ng/mL, while those in the tumors varied from about 0 to 1000 ng/mL. Exogenously added NM23-H1 protein did not affect the growth or survival of various leukemia and lymphoma cell lines. However, NM23-H1 protein inhibited the survival of adherent normal peripheral blood mononuclear cells (PBMNC) at 100–1000 ng/mL, and slightly stimulated the survival of nonadherent PBMNC. These results suggest that the effect of NM23-H1 protein on normal PBMNC may be associated with a poor prognosis in hematological malignancies.     

Physiological relevance and functional potential of central nervous system-derived cell lines

Central nervous system (CNS)-derived neural cell lines have proven to be extremely useful for delineating mechanisms controlling such diverse phenomena as cell lineage choice and differentiation, synaptic maturation, neurotransmitter synthesis and release, and growth factor signalling. In addition, there has been hope that such lines might play pivotal roles in CNS gene therapy and repair. The ability of some neural cell lines to integrate normally into the CNS following transplantation and to express foreign, often corrective gene productsin situ might offer potential therapeutic approaches to certain neurodegenerative diseases. Five general strategies have evolved to develop neural cell lines: isolation and cloning of spontaneous or mutagenically induced malignancies, targeted oncogenesis in transgenic mice, somatic cell fusion, growth factor mediated expansion of CNS progenitor or stem cells, and retroviral transduction of neuroepithelial precursors. In this article, we detail recent progress in these areas, focusing on those cell lines that have enabled novel insight into the mechanisms controlling neuronal cell lineage choice and differentiation, both in vitro and in vivo.     

Proteinoids as complexes of polyamino acids with melanoidins

Proteinoids have been demonstrated as complexes of amino acid polymers with melanoidin pigments. Some physico-chemical properties of proteinoid pigments were studied in comparison with the standard melanoidins. Proteinoid pigments were able to enhance oxidoreduction and hydrolysis reactions, and their activity was comparable with the activity of the corresponding polyamino acid components or even of the entire proteinoids. The pigmented proteinoids had relatively strong ESR signal indicating the presence of free radicals into melanoidin components. Hypothetical participation of proteinoid melanoidin pigments in prebiotic evolution is discussed.     

Physiological relevance of the endogenous mono(ADP-ribosyl)ation of cellular proteins

The mono(ADP-ribosyl)ation reaction is a post-translational modification that is catalysed by both bacterial toxins and eukaryotic enzymes, and that results in the transfer of ADP-ribose from betaNAD+ to various acceptor proteins. In mammals, both intracellular and extracellular reactions have been described; the latter are due to glycosylphosphatidylinositol-anchored or secreted enzymes that are able to modify their targets, which include the purinergic receptor P2X7, the defensins and the integrins. Intracellular mono(ADP-ribosyl)ation modifies proteins that have roles in cell signalling and metabolism, such as the chaperone GRP78/BiP, the beta-subunit of heterotrimeric G-proteins and glutamate dehydrogenase. The molecular identification of the intracellular enzymes, however, is still missing. A better molecular understanding of this reaction will help in the full definition of its role in cell physiology and pathology.     

Cellular and tissue distribution of potassium: Physiological relevance,mechanisms and regulation

Potassium (K⁺) is the most important cationic nutrient for all living organisms. Its cellular levels are significant (typically around 100 mM) and are highly regulated. In plants K⁺ affects multiple aspects such as growth, tolerance to biotic and abiotic stress and movement of plant organs. These processes occur at the cell, organ and whole plant level and not surprisingly, plants have evolved sophisticated mechanisms for the uptake, efflux and distribution of K⁺ both within cells and between organs.     

The metabolism of dietary polyphenols and the relevance to circulating levels of conjugated metabolites

Berry extracts rich in anthocyanins have been linked to protective effects including the modulation of age-related neurological dysfunction and the improvement of the resistance of red blood cells against oxidative stress in vitro . In this study the bioavailability, metabolism and elimination of polyphenols from blackcurrant juice, rich in anthocyanins, flavonols, and hydroxycinnamates, were investigated. The four major native anthocyanidin glycosides of blackcurrant juice, delphinidin-3-glucoside, delphinidin-3-rutinoside, cyanidin-3-glucoside and cyanidin-3-rutinoside, were detected and identified in low amounts by HPLC and LC-MS in plasma and urine post-ingestion. Elimination of the anthocyanins was fast (maximum excretion after 1 h) and plasma levels (0-128.6 nmol/l) and total urinary excretion (0.07-1.35 mg; 0.007-0.133% of the dose ingested) were low. Most significantly, of the hydroxycinnamates, conjugated and free ferulic, isoferulic, p -coumaric, sinapic and vanillic acids were identified in plasma and urine, using GC-MS techniques. Quercetin and kaempferol (as glucuronides) and the proposed colonic metabolite of quercetin, 3-hydroxyphenylacetic acid, were detectable in a minority of subjects. Increased daily urinary hippuric, 4-hydroxyhippuric and 3-hydroxyhippuric acid levels were also observed post-ingestion in all volunteers.     

Physiological relevance of successive hydroxylations of toluene by toluene para-monooxygenase of Ralstonia pickettii PKO1

We have recently found that toluene para-monooxygenase (TpMO) of Ralstonia pickettii PKO1 (encoded by tbuA1UBVA2C) performs successive hydroxylations of benzene (Appl. Environ. Microbiol. 70: 3814, 2004) as well as hydroxylates toluene to a mixture of 90% p-cresol and 10% m-cresol which are then further oxidized to 100% 4-methylcatechol (J. Bacteriol. 186: 3117, 2004) whereas it was thought previously that TpMO forms 100% m-cresol and is not capable of successive hydroxylations. Here we propose a modification of the degradation pathway originally described by Olsen et al. (J. Bacteriol. 176: 3749, 1994) that now relies primarily on TpMO for conversion of toluene to 4-methylcatechol (instead of m-cresol) since both m-cresol and p-cresol are shown here to be good substrates for Escherichia coli expressing TpMO (V_max/K_m=0.046, 0.036, and 0.055 mL min^-1 mg^-1 protein for the oxidation of toluene, m-cresol, and p-cresol, respectively). In light of the broader activity of TpMO, phenol hydroxylase (encoded by tbuD) appears to facilitate conversion of any m-cresol or p-cresol formed from toluene oxidation by TpMO to 4-methylcatechol; hence, the cell has a redundant method for making this important intermediate 4-methylcatechol. Further, it is suggested that the physiological relevance of the 10% m-cresol formed from toluene oxidation by TpMO is needed for induction of the meta cleavage operon tbuWEFGKIHJ to enable full metabolism of toluene since p-cresol (and o-cresol) do not induce the meta-cleavage pathway. Therefore both the successive hydroxylation of toluene by TpMO and the product distribution are of physiological relevance to the cell.     

Physiological relevance of successive hydroxylations of toluene by toluene para-monooxygenase of Ralstonia pickettii PKO1

We have recently found that toluene para-monooxygenase (TpMO) of Ralstonia pickettii PKO1 (encoded by tbuA1UBVA2C) performs successive hydroxylations of benzene (Appl. Environ. Microbiol. 70: 3814, 2004) as well as hydroxylates toluene to a mixture of 90% p-cresol and 10% m-cresol which are then further oxidized to 100% 4-methylcatechol (J. Bacteriol. 186: 3117, 2004) whereas it was thought previously that TpMO forms 100% m-cresol and is not capable of successive hydroxylations. Here we propose a modification of the degradation pathway originally described by Olsen et al. (J. Bacteriol. 176: 3749, 1994) that now relies primarily on TpMO for conversion of toluene to 4-methylcatechol (instead of m-cresol) since both m-cresol and p-cresol are shown here to be good substrates for Escherichia coli expressing TpMO (V_max/K_m=0.046, 0.036, and 0.055 mL min^?1 mg^?1 protein for the oxidation of toluene, m-cresol, and p-cresol, respectively). In light of the broader activity of TpMO, phenol hydroxylase (encoded by tbuD) appears to facilitate conversion of any m-cresol or p-cresol formed from toluene oxidation by TpMO to 4-methylcatechol; hence, the cell has a redundant method for making this important intermediate 4-methylcatechol. Further, it is suggested that the physiological relevance of the 10% m-cresol formed from toluene oxidation by TpMO is needed for induction of the meta cleavage operon tbuWEFGKIHJ to enable full metabolism of toluene since p-cresol (and o-cresol) do not induce the meta-cleavage pathway. Therefore both the successive hydroxylation of toluene by TpMO and the product distribution are of physiological relevance to the cell.     

Physiological relevance of plant 2‐Cys peroxiredoxin overoxidation level and oligomerization status

Peroxiredoxins are ubiquitous thioredoxin‐dependent peroxidases presumed to display, upon environmental constraints, a chaperone function resulting from a redox‐dependent conformational switch. In this work, using biochemical and genetic approaches, we aimed to unravel the factors regulating the redox status and the conformation of the plastidial 2‐Cys peroxiredoxin (2‐Cys PRX) in plants. In Arabidopsis, we show that in optimal growth conditions, the overoxidation level mainly depends on the availability of thioredoxin‐related electron donors, but not on sulfiredoxin, the enzyme reducing the 2‐Cys PRX overoxidized form. We also observed that upon various physiological temperature, osmotic and light stress conditions, the overoxidation level and oligomerization status of 2‐Cys PRX can moderately vary depending on the constraint type. Further, no major change was noticed regarding protein conformation in water‐stressed Arabidopsis, barley and potato plants, whereas species‐dependent up‐ and down‐variations in overoxidation were observed. In contrast, both 2‐Cys PRX overoxidation and oligomerization were strongly induced during a severe oxidative stress generated by methyl viologen. From these data, revealing that the oligomerization status of plant 2‐Cys PRX does not exhibit important variation and is not tightly linked to the protein redox status upon physiologically relevant environmental constraints, the possible in planta functions of 2‐Cys PRX are discussed.     

Physiological adaptations to a weight-loss dietary regimen and exercise programs in women

Kraemer, William J., Jeff S. Volek, Kristine L. Clark, ScottE. Gordon, Thomas Incledon, Susan M. Puhl, N. Travis Triplett-McBride, Jeffrey M. McBride, Margot Putukian, and Wayne J. Sebastianelli. Physiological adaptations to a weight-loss dietary regimen andexercise programs in women. J. Appl.Physiol. 83(1): 270-279, 1997.Thirty-one women(mean age 35.4 ± 8.5 yr) who were overweight were matched andrandomly placed into either a control group (Con; n = 6), a diet-only group (D;n = 8), a diet+aerobic endurance exercise training group (DE; n = 9),or a diet+aerobic endurance exercise training+strength training group(DES; n = 8). After 12 wk, the threedietary groups demonstrated a significant(P  0.05) reduction in body mass,%body fat, and fat mass. No differences were observed in the magnitudeof loss among groups, in fat-free mass, or in resting metabolic rate.The DE and DES groups increased maximal oxygen consumption, and the DESgroup demonstrated increases in maximal strength. Weight loss resultedin a similar reduction in total serum cholesterol, low-densitylipoprotein cholesterol, and high-density lipoprotein cholesterol amongdietary groups. These data indicate that weight loss during moderatecaloric restriction is not altered by inclusion of aerobic oraerobic+resistance exercise, but diet in conjunction with training caninduce remarkable adaptations in aerobic capacity and muscular strengthdespite significant reductions in body mass.